Schizophrenia (SZ) is a common, severe disorder for which treatment is inadequate and unpredictable at present. Its causation is uncertain. Its lifetime prevalence is approximately 1% world-wide. It is estimated that there are approximately 2.2 million SZ patients in the USA at present and over twice this number in India. As it is a lifetime condition, SZ entails enormous morbidity and public health costs, world-wide. Cognitive impairment is a key disabling feature of SZ. The impairment affects functional outcome and employability, resulting in increased burden. Currently, medications offer only modest benefits for the cognitive dysfunction. Hence, non- pharmacological interventions are worth consideration. Yoga is known to enhance cognitive abilities in healthy persons. Our preliminary studies have shown for the first time that there may be remarkable improvement in selected cognitive domains among outpatients with SZ. The improvement is unlikely to be due to rater bias, as they were noted using a computerized neurocognitive battery. Since our preliminary studies involved an open trial, it is necessary to conduct more controlled studies. To evaluate our results further, we propose to test the effectiveness of yoga supplementation using a controlled single blind design in India. Outpatients with SZ (N=258) undergoing treatment at a large academic center in New Delhi, India will be randomly assigned to one of the three groups- yoga training (YT, N=86), physical exercise (PE, N=86) or treatment as usual (TAU, N=86). The YT group will undergo 21 days yoga supplementation, while the PE group will complete a 21 day systematic physical exercise training regime. The third group will have no such supplementation. All patients will receive appropriate medications and counseling. Cognitive state, symptom severity and overall function will be assessed at four time points: just before, immediately after, three months later and six months after completion of YT/PE supplementation. The evaluations will be conducted by raters blind to group status. Thus, we will test a novel method to supplement the beneficial effects of pharmacotherapy more rigorously than in our pilot studies. Demonstrable benefits from YT will motivate further studies to test other important issues, such as dose effects of YT, its temporal benefits and its interaction with medications. PUBLIC HEALTH RELEVANCE: The proposed studies may lead to better treatment for schizophrenia using the ancient practice of Yoga. Our preliminary studies suggest significant beneficial effects of Yoga on cognitive function, which can be severely impaired in schizophrenia. The cognitive impairment is difficult to treat at present using medications.